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This study was supported by the Sir Charles Gairdner Hospital Research Fund and by the Sir Charles Gairdner Hospital Intensive Care Research Fund.

The work was performed at the Large Animal Facility of the University of Western Australia, Perth, Australia.

Abstract

Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. Randomized levels of IAP (3 [baseline], 18, and 26 mmHg) were applied, with levels of PEEP (5, 8, 12, and 15 cmH2O) applied randomly at each IAP level. We measured bladder pressure (IAP), superior vena cava pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, FVP, mixed venous oxygen saturation (Svo2), and Sfvo2. We found that FVP correlated well with IAP (FVP = 4.1 + [0.12 × PEEP] + [1.00 × IAP]; R2 = 0.89, P < 0.001) with a moderate bias and precision of 5.0 and 3.8 mmHg, respectively. Because the level of agreement did not meet the recommendations of the World Society of Abdominal Compartment Syndrome, FVP cannot currently be recommended to measure IAP, and further clinical trials are warranted. However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.

INTRODUCTION

Central venous access is widely used in critically ill patients for the administration of drugs and for the purpose of monitoring the central venous pressure and venous oxygen levels (1). However, where puncture of the internal jugular vein or the subclavian vein is either not possible or is deemed unsafe, femoral venous access is often performed. This is especially the case in emergencies or in the setting of pediatric, obese, and burns patients, where femoral venous access provides simple, safe, and fast venous access into a large-caliber vein (2-5).

Despite recognized limitations (6), central venous pressure is often measured to assess the fluid status of shocked patients and to assess their response to fluid therapy (1). Intra-abdominal hypertension (IAH), defined by the World Society of Abdominal Compartment Syndrome (WSACS) as a sustained or repeated pathologic elevation of the intra-abdominal pressure (IAP) to 12 mmHg or greater, is common in critically ill patients and is associated with a high morbidity and mortality (7-10).

There are conflicting reports with regard to whether femoral venous pressure (FVP) will reflect superior vena cava pressure (SVCP) or IAP in the setting of IAH (2, 3, 11-18). Furthermore, FVP is currently not recommended by WSACS as a surrogate measure of IAP (7, 19).

Positive end-expiratory pressure (PEEP) has been suggested to counteract the formation of atelectasis in the presence of IAH (20, 21). The influence of PEEP on SVCP is well established. However, the influence of PEEP on FVP is less clear. Because potentially IAP and PEEP can independently influence the "central" venous pressure, we studied the influence of different levels of IAP and also of different levels PEEP on SVCP, pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP), and FVP in a pig model of IAH. We hypothesized that FVP will reflect IAP and might be used as a surrogate measure of IAP.

Furthermore, we investigated the role of femoral venous oxygen saturation (Sfvo2) in the setting of IAH by assessing the correlation of Sfvo2 with mixed venous oxygen saturation (Svo2), cardiac output (CO), and abdominal perfusion pressure (APP). These measurements were made, and these data were collected as part of another study investigating the effects of IAP and PEEP on cardiovascular and respiratory parameters (22).

MATERIALS AND METHODS

The study conformed to the regulations of the Australian code of practice for the care and use of animals for scientific purposes and was approved by the Animal Ethics Committee of the University of Western Australia.

Anesthesia, mechanical ventilation, surgical preparation, instrumentation, and measurements were performed as previously described (22) and as briefly outlined in the following sections.

Anesthesia

Thirteen large white-breed pigs (mean animal weight was 42 [SD, 8] kg) were weighed and sedated according to a standardized protocol involving intramuscular zolazepam/tiletamine (Zoletil) and xylazine to facilitate obtaining auricular venous access. Anesthesia was subsequently established using propofol boluses, and the animals were intubated using a cuffed oral endotracheal tube with position confirmed using quantitative end-tidal CO2 monitoring. Anesthesia was maintained using propofol (9-36 mg/kg i.v. per hour), morphine (0.1-0.2 mg/kg i.v. per hour), and ketamine (0.3-0.6 mg/kg i.v. per hour). An intravenous colloid bolus was administered at induction of anesthesia followed by a slow infusion (Gelofusine [Braun, Oss, the Netherlands], 500 mL over 30 min followed by 1 mL/kg per hour). At the end of the experimental protocol, the pigs were killed with intravenously administered pentobarbitone.

Ventilation

Ventilation was maintained in a volume-controlled mode with a tidal volume of 8 mL/kg, initial PEEP of 5 cmH2O, and Fio2 of 0.4. Respiratory rate was adjusted to maintain an end-tidal CO2 between 35 and 45 mmHg.

Measurements

Throughout the study, the animals remained in the supine position. Hemodynamic monitoring included femoral arterial and venous cannulas and a right internal jugular venous sheath and pulmonary artery catheter (ES-04301, CS-15851-E, SI-09806, and AH-05050; Arrow International, Reading, Pa). The femoral venous line had a 15-cm intra-abdominal length, and an intra-abdominal position was confirmed by assessing pressure response during manual external abdominal compression. MAP, SVCP, PAP, PAOP, and FVP were measured, and mean values were recorded.

Pressures were measured with a standard transducer system (Hospira, Lake Forest, Ill) and monitored with a Sirecust 126 critical care monitor (Siemens Medical Electronics, Danvers, Mass). Mean pressures were measured from the midaxillary line, with the pigs in the supine position (7).

Experimental protocol

Baseline measurements were recorded. The order of abdominal balloon inflation (IAP) and the application of PEEP were randomized using a spit plot design with randomized complete blocks and main plots (24). The abdominal balloon was either not inflated (baseline IAP) or inflated with air to IAP of 18 ± 2 mmHg (grade II IAH) or 26 ± 2 mmHg (grade IV IAH), where the WSACS has defined IAH grades as follows: grade I, IAP = 12 to 15 mmHg; grade II, IAP = 16 to 20 mmHg; grade III, IAP = 21 to 25 mmHg; and grade IV, IAP is greater than 25 mmHg. Thereafter, PEEP was applied at 5, 8, 12, or 15 cmH2O (3.7, 5.9, 8.8, and 11.0 mmHg, respectively) at each level of IAP. At the end of each IAP, the intra-abdominally placed balloon was shortly released, allowing the IAP to reach baseline values before the IAP was adjusted to the next randomly assigned IAP. A standardized lung recruitment maneuver was performed at each IAP and PEEP setting (22, 25). Measurements were taken after 5 min to enable stabilization.

Statistics

Sample size calculations were performed for a previously published experiment (22). Post hoc calculated power was 97% to detect a difference in FVP of 3 mmHg (mean FVP of 7 [SD, 2] mmHg) between two different IAP settings (α = 0.05, power = 80%). Application of the Kolmogorov-Smirnov test showed the data to be normally distributed, and hence, data are reported as mean (SD). An ANOVA for repeated measures was used to compare measured values between different levels of PEEP and IAP. A post hoc Student-Newman-Keuls test was used to adjust for multiple comparisons. P < 0.05 was considered statistically significant. Linear regression analysis was used to examine the relationship between Sfvo2 and Svo2, CO, and APP. Multiple linear regression analysis was used to examine the relationship between FVP, SVCP, PAP, and PAOP and PEEP and IAP. A Bland-Altman assessment for agreement was used to compare bladder pressure and FVP. Bias and precision (SD of bias) were calculated.

Effects of IAP on SVCP, PAP, PAOP, and FVP

The effects of IAP and PEEP on SVCP, PAP, PAOP, and FVP are shown in Figures 1 and 2. At baseline IAP, there were no significant differences between SVCP and FVP. Intra-abdominal pressure had a large influence on FVP and only a small influence on SVCP, PAP, and PAOP.

Effects of PEEP on SVCP, PAP, PAOP, and FVP

The application of PEEP was associated with an increase in SVCP only in the presence of raised IAP but not at baseline IAP (Fig. 1). In contrast, PEEP was associated with an increase in FVP at baseline IAP but not in the presence of IAH (Fig. 1). Positive end-expiratory pressure was associated with an increase in PAP and PAOP (Fig. 2).

DISCUSSION

Summary of findings

We found that, in the absence of IAH, FVP is equal to SVCP. However, in the presence of IAH, FVP increases proportional to IAP. Positive end-expiratory pressure did not influence FVP but influenced SVCP, PAOP, and PAP. To our knowledge, this is the first study assessing the influence of IAP and PEEP on FVP and SVCP and whether Sfvo2 correlates with APP.

Can FVP be used to assess central venous pressure? The role of IAP and PEEP

Because femoral venous cannulation is generally considered safe and simple, it is widely used especially in the emergency setting and in pediatric patients (2-5). A clear correlation between SVCP and right atrial pressure has been shown previously (26, 27). However, there has been some controversy with regard to the correlation of FVP with SVCP and whether IAP influences FVP.

In our study, and in agreement with previous findings, in the absence of IAH, FVP correlated well with SVCP (Fig. 1) (4, 12, 26-29). However, in the presence of IAH, we found that FVP did not reflect SVCP as FVP was highly influenced by IAP. There are conflicting reports in the literature whether IAP influences FVP (2, 3, 11-18, 30).

One explanation for not finding the IAP to influence FVP is that the FVP reading will be dependent on the anatomical placement of the catheter tip in relation to abdominal vascular zones as previously described (30). When the tip of the femoral catheter lies within the proximity of the right atrium, the pressures will correlate well with SVCP independently of IAP (11, 30). However, when using a short catheter with the catheter tip lying in the abdomen (venous pressure upstream to IAP), there will be a close correlation between FVP and IAP (14-18, 30) but not with SVCP. Other explanations include that the studies were either underpowered or only patients with low-grade IAH were included (3, 12).

Except at baseline, PEEP only minimally (not statistically significant) influenced FVP (Table 1, Fig. 1). The nearly absent effect of PEEP on FVP in the presence of IAH can be explained by the reduced estimated transpulmonary end-expiratory pressures (PEEP − IAP), which would have approximated −7 and −15 mmHg at PEEP of 15 cmH2O (11.0 mmHg) at IAPs of 18 mmHg (grade II IAH) and 26 mmHg (grade IV IAH), respectively (22). However, in the absence of IAH and without an obstruction to flow, the FVP reflected the SVCP well and was therefore strongly influenced by PEEP.

In summary, a low FVP is likely to reflect SVCP accurately in the absence of IAH, whereas a high FVP may be the result of a raised SVCP or IAP. Positive end-expiratory pressure did not relevantly influence FVP except in the absence of IAH.

How did IAP and PEEP influence SVCP?

Superior vena cava pressure has not only been shown to poorly predict fluid responsiveness (6), but in the setting of IAH, there exists an inverse ratio between SVCP and venous return (13, 31).

In our study, SVCP was more affected by PEEP than by IAP. The pressure transmission (in mmHg) to the SVCP caused by PEEP (measured in cmH2O) was approximately 50% (Table 1, Fig. 1), which compares with other studies (32).

Superior vena cava pressure was also influenced by IAP but to a lesser degree (approximately 20%). However, the suggested linear relationship between the influence of IAP on SVCP might not truly represent the influence of IAP on SVCP because when analyzing data of previous studies, the influence of IAP on SVCP does not seem to be linear (13, 17, 31).

In summary, the SVCP was more influenced by PEEP than by IAP. The fact that both PEEP and IAP influenced SVCP needs to be considered not only in the research setting but also in clinical situations, especially when assessing the fluid status of a patient in the light of the inverse relationship between SVCP and venous return in the setting of increased PEEP and increased IAP.

How did IAP and PEEP influence PAOP and PAP?

We found that PAOP and PAP were influenced significantly by IAP and by PEEP to a degree that was comparable to how SVCP was influenced (Table 1, Figs. 1 and 2). However, the differences were not substantial, which is similar to other experimental studies (33). It is not surprising that SVCP, PAOP, and PAP were influenced similarly by PEEP and IAP, as all three pressures are measured within the intrathoracic cavity.

Can FVP be used as a surrogate measure of IAP?

Currently, measuring bladder pressure is considered the clinical criterion standard in patients with known or suspected IAH as it is easy to use and shows reasonable agreement with direct IAP measurements (7). Femoral venous pressure as a measure of IAP is not currently recommended by the WSACS because of conflicting data on the correlation between FVP and IAP (7, 19). However, we found a 1:1 relationship with strong correlation (R2 = 0.89) between the FVP and the bladder pressure.

Why we found a bias of 5 mmHg between the FVP and the bladder pressure is not clear. This is in keeping with the literature, for example, Gudmundsson et al. (17) also found a higher FVP than bladder pressure.

We want to point out that the porcine urinary bladder is intraperitoneal as opposed to the human bladder that is extraperitoneal (17). In theory, measuring the bladder pressure as a surrogate measure of IAP is, according to the Pascal law, measuring a pressure within a closed cavity, where the pressures will be equal to any other point within the closed cavity (7). Therefore, at least in theory, the position of the bladder, whether retroperitoneal (humans) or intraperitoneal (pigs, sheep, dogs, rabbits, and rats), should not influence the pressure reading. If anything, an intraperitoneal bladder should allow a more accurate IAP measurement than a retroperitoneal bladder.

The higher FVP in comparison to the bladder pressure could be explained by the FVP in the setting of IAH, which would be a composition of the following two pressures: the mean circulatory filling pressure as described by Guyton et al. (34) in addition to the IAP or as a rule of thumb: FVP = SVCP (uninfluenced by PEEP and IAP) + IAP. However, when we tested this hypothesis, we failed to find a sufficient correlation or sufficient level of agreement on a Bland-Altman plot (not shown).

The FVP, when compared with the bladder pressure, failed to meet the WSACS recommended bias and precision of 1 and 2 mmHg, respectively (35). A number of reasons may have led to this moderate precision. First, we did not measure the pressures at end expiration as recommended by the WSACS (7). Second, the reliability of bladder pressure to correctly measure IAP has been questioned because of a high variability in measurements (19).

Indeed, most studies in humans have compared the bladder pressures with laparoscopy pressures (often poorly defined) and also found a variable degree of bias and precision. For example, Fusco et al. (36) (n = 37 patients) found a mean bias and precision of −3.8 and 4.9 mmHg (i.e., the urinary bladder pressure was 3.8 mmHg higher than the directly measured IAP), and Johna et al. (37) found a mean bias and precision of −7.9 and 3.9 mmHg, respectively. In our study, we found a comparable bias and precision (5 and 3.6 mmHg, respectively). Importantly, the bias and precision currently recommended by the WSACS would exclude the urinary bladder pressure to pass the test of validation.

In contrast to this, only a few studies compared direct with indirect measurements of IAP using a comparable pressure measurement technique and accordingly found a good level of agreement. For example, De Potter et al. (38) found in vitro a mean bias and precision of 0.1 and 0.4 mmHg; Schachtrupp et al. (39) found in a porcine model a mean bias and precision of 0.5 and 2.6 mmHg; and Iberti et al. (40) found a mean bias and precision of −0.7 and 1.7 mmHg, respectively.

In summary, FVP was only minimally influenced by PEEP in the presence of IAH. Femoral venous pressure closely correlated with bladder pressure. However, we cannot currently recommend the use of FVP as a surrogate measure of IAP, as the bias and precision are more than recommended by the WSACS. A raised FVP, however, should prompt the measurement of bladder pressure to exclude IAH. Further research investigating whether FVP can be used in the clinical setting is warranted.

Femoral venous oxygen saturation and its clinical use

Targeting Svo2 has been used successful in the early management of patients in septic shock and has been shown to improve outcome (1). There is currently no simple means to detect insufficient abdominal vascular perfusion. We therefore assessed whether the Sfvo2 would be useful in assessing the balance between oxygen delivery and oxygen demand in the setting of IAH, as this has never been investigated before. It has been suggested to target APP in patients with IAH, as this has been associated to positively influence outcome (8, 41).

In our study, the mean Sfvo2 was similar to the mean Svo2 at all IAP and PEEP settings (Table 2). However, in agreement with other studies (3, 42), we found a poor correlation (regression analysis) between Svo2 and Sfvo2 when considering all individual values (see Results). As we did not measure abdominal perfusion but only APP, we cannot exclude a possible relationship between Sfvo2 and abdominal perfusion, and this would need to be further investigated.

However, as we were unable to find a correlation between Sfvo2 and either CO or APP, we currently cannot recommend Sfvo2 as a useful measurement regardless of the presence or absence of IAH.

Limitations

We used pigs in this study because pig models have been used extensively in IAH research and because the cardiorespiratory physiology of this animal is very similar to humans. However, extrapolation of animal data to clinical practice must be performed with caution, and it has to be emphasized that the anatomical position of the bladder is retroperitoneal in humans as opposed to being intraperitoneal in most experimental animals including pigs (17).

A further limitation to our study is that we measured the mean IAP instead of the end-expiratory IAP as suggested by WSACS (7). However, as all pigs received standardized mechanical ventilation, the differences between the mean and end-expiratory pressures would have affected all measurements equally and cannot explain the low level of agreement between FVP and bladder pressure.

CONCLUSIONS AND CLINICAL IMPLICATIONS

In conclusion, in the absence of IAH, FVP correlated well with SVCP, and in the presence of IAH, FVP correlated well with IAP. Positive end-expiratory pressure only minimally (not significantly) influenced FVP, except in the absence of IAH. Superior vena cava pressure was influenced more by PEEP than by IAP.

Because the moderate bias and precision were found to not meet the recommended limits of WSACS (35), FVP cannot currently be recommended to assess IAP, and further clinical validation of FVP to measure IAP should be encouraged. It has to be emphasized that a raised FVP should prompt the measurement of the bladder pressure.

As Sfvo2 does not correlate with Svo2, CO, and APP, we do not currently recommend the measurement of Sfvo2, irrespective of the presence or absence of IAH.

ACKNOWLEDGMENTS

The authors thank the Department of Anesthesia of the Sir Charles Gairdner Hospital for the logistical support. They also thank Dr Richard Parsons, senior lecturer in statistics, Curtin University, Perth, for statistical assistance; the Department of Medical Technology and Physics at the Sir Charles Gairdner Hospital; and the team of the Large Animal Facility of the University of Western Australia for technical assistance.

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